Background: The optimal invasive treatment for sciatica secondary to a herniated lumbar disc (HLD) remains controversial with a paucity of evidence for non-surgical treatments such as transforaminal epidural steroid injection (TFESI) compared to surgical microdiscectomy (surgery). Nerves compares the clinical and cost-effectiveness of microdiscectomy and TFESI for management of radicular pain. Methods: Nerves is a pragmatic multi-centre, randomised, unblinded, prospective trial recruiting from 11 UK spinal units. Eligible patients with non-emergency sciatica secondary to a HLD, aged between 16 and 65 years and who failed conservative care and had symptoms for <12 months were randomly assigned 1:1 to receive surgery or TFESI using an online randomisation system stratified by centre and used block randomisation, with random variable block length. Allocations were concealed from investigators and participants prior to recruitment. The primary efficacy outcome (PO) was the Oswestry Disability Questionnaire (ODQ) at 18 weeks post-randomisation. All randomised participants who completed valid ODQ at baseline and 18 weeks were including in the analysis by intention-to-treat. Safety analysis included all treated participants. Cost-effectiveness was estimated from the EQ-5D-5L, Hospital Episode Statistics, medication usage and self-report resource-use data. The trial was registered with ISRCTN04820368 and EudraCT number: 2014-002751-25. The trial is closed to recruitment and follow up completed. Findings: Between Mar 6, 2015 and Dec 21, 2017, 163 participants were randomised to surgery (n=83) or TFESI (n=80). No significant differences were found in ODQ for surgery versus TFESI. Mean improvement for surgery 26.7 points (standard deviation (SD) 21.35), TFESI 24.5 points (SD 18.89); estimated treatment difference -4.25 (95% CI -11.09 to 2.59) p=0.22). There were 4 (3.8%) serious adverse events (SAEs) associated with surgery, and none with TFESI. Compared to TFESI, surgery had an incremental cost-effectiveness ratio of £38,737 per quality-adjusted life-year (QALY) gained, and a probability of 0.17 of being cost-effective at a willingness to pay threshold of £20,000 per QALY. Interpretation: For patients with sciatica secondary to HLD with duration less than 1 year, TFESI should be considered as a first invasive treatment option. Surgery is unlikely to be a cost-effective alternative to TFESI.